Osteoporosis
The World Health Organization ranks osteoporosis just below cardiovascular disease as a public health concern. Recent statistics indicate that approximately 75 million Americans, Europeans and Japanese are affected by osteoporosis, including one third of women 60-70 and two thirds of women in their 80's or above. Twenty-one million women have been diagnosed with osteopenia (low bone mass) while about eight million American women have osteoporosis. Over one million fractures are attributed to individuals with osteoporosis.
Conventional radiographs are not sensitive enough to detect osteoporosis until bone density mineral has been reduced by over 50%. Dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography are the most widely used methods for detecting osteoporosis. The cytokines responsible for bone loss include RANKL (receptor activated nuclear Kappa ligand) and osteoprotegerin as well as agents such as MIP 1a (macrophage inflammatory protein alpha) and alkaline phosphatase. In essence some of the same markers that relate to bone loss in periodontal disease are associated with bone loss in osteoporosis. Laboratory tests used to diagnose osteoporosis have relied on markers that include osteocalcin and bone alkaline phosphatase. These markers are detected in blood samples and are not currently used as diagnostic tests.
Osteoporosis is seen as a “silent” risk factor for bone fracture. Bone mineral density testing is recommended for all post menopausal women younger than 65 who have one additional risk factor for osteoporosis beyond menopause.
Periodontal Disease
Periodontal disease is another disease whose end point is bone loss. Periodontal disease is an inflammatory disease that begins as an inflammation of the gingival soft tissues (gums) and then proceeds to affect the supporting structures of the tooth in its boney socket. At present periodontal disease is the most pressing dental malady that if untreated can result in tooth loss. Further, recent evidence suggests that this chronic dental infection that results in widespread oral inflammation can contribute to an increased risk for systemic complications including an increased risk for heart disease. With the discovery of fluoride and the resulting reduction in the prevalence of caries, periodontal disease and its earliest manifestation gingivitis has become the most prevalent and costly of dental infections. Gingivitis and its sequelae, periodontal disease affects over 50% of the adult population.
Oral bacteria form a plaque biofilm that can initiate gingival inflammation. Under the appropriate circumstances gingivitis can lead to periodontitis which is manifested as an inflammatory induced destruction of the honey support of the teeth. The disease is pandemic, costly, can result in tooth loss, and is also conjectured to increase the risk for coronary heart disease and other systemic conditions.
Currently the existing technology used by a dentist or dental health professional to detect periodontal disease relies on a clinical examination that includes a periodontal probe and/or an x-ray. It is well known that these methods are imperfect because they are operator sensitive, time consuming and detect past history of tissue destruction. Thus there remains a need for improved ways of detecting periodontal disease.
Bone loss, the ultimate proof of disease, is measured by radiograph and is an end stage of disease, which for the most part is irreversible. The periodontal complex is best described as a peg in a socket, the tooth represented by the peg and the alveolus, or surrounding bone, represented by the socket. The tooth is connected to its socket by fibers made of collagen that enable the tooth to respond to the forces of mastication and clenching and grinding. Inflammation causes bone loss which occurs by virtue of osteoclasts (bone eating cells) which eat away the bone, widen the socket, leading the affected tooth to become loose and ultimately non-functional. Bone loss of the periodontal tissues takes anywhere from 6-18 months to manifest itself.
Longitudinal models of infectious diseases are capable of providing insights into tissue destructive events provoked by infectious agents. For example Agace et al. have documented the initial inflammatory response in humans to Escherichia coli that provoke urinary tract infections. Most studies of pathogenesis have been relegated to animal models of disease which while useful have their own limitations. Very few prospective studies of human periodontal disease have been undertaken. Over the past several years our group, and others, (Bueno et al 1999) have been working on a longitudinal model of a particular form of periodontal disease found in children called localized aggressive periodontitis (LAP). As a longitudinal model of periodontal disease, LAP has several advantages. First, since periodontal disease is unusual in children and because of a distinctive molar/incisor pattern of distribution, LAP is relatively simple to diagnose. Second, there is convincing evidence that a particular microbe, Aggregatibacter actinomycetemcomitans infects those children who have LAP. Moreover, since the disease progresses rapidly, breakdown can occur between 1-3 years. Thus, it is possible to study LAP over a relatively short period of time as compared to chronic adult periodontitis which advances slowly over an undetermined time period. Recently two longitudinal studies have been done utilizing populations at risk for LAP. Both studies have shown that A. actinomycetemcomitans carriers are at risk; but neither reported on host factors related to LAP onset.
Diagnosis of periodontal disease is initially based on measurements of soft tissue detachment from the tooth, which results in a periodontal pocket. Methods used to probe for attachment loss and to detect bone loss, the hallmark of the irreversible stage of periodontal disease, while quite specific are not very sensitive, and often delay diagnosis. A number of scientific advances have spawned technologies that are capable of detecting nanograms or picograms levels of inflammatory markers in bodily fluids. These technologies could potentially be used to develop into tests for early clinical diagnosis, which if successful could provide earlier warning of disease onset as compared to the relatively insensitive methods used currently. However, to date many of the candidate biomarkers that have been tested have not been able to distinguish between forms of gingivitis that are reversible, and periodontitis that is irreversible. New biomarkers are required but cannot be developed in the absence of a longitudinal model of disease.